LHON is a mitochondrial disease. It is usually caused by one of several pathogenic genetic mutations in the mitochondria. Those who have a mitochondrial LHON mutation without vision loss are referred to as “carriers” or "unaffected carriers." In some individuals who carry an LHON mutation, the optic nerves suddenly begin to swell then atrophy. This causes a disruption in the signals between the eyes and the brain, leading to vision loss. Those who have central vision loss due to LHON are referred to as “affected.”
The most common LHON mutation is the 11778 (ND4) mutation, causing over 65% of all LHON cases. Most of the remaining LHON cases are caused by the 14484 (ND6) and 3460 (ND1) mutations. Several very rare mitochondrial mutations cause most of the other cases. Recently some nuclear mutations that impact the mitochondria, including DNAJC30, have been associated with LHON vision loss.
At the 2014 LHON Conference, Dr. Valerio Carelli discussed what may influence the risk of onset of vision loss in individuals carrying an LHON mutation. Dr. Alfredo Sadun discussed Environmental Factors at the 2021 LHON Conference. The Gene-Environment Interactions article provides additional information.